Actemra® (tocilizumab) (Intravenous) Document Number: MODA-0002 Last Review Date: 10/26/2020 Date of Origin: 09/21/2010 Dates Reviewed: 12/2010, 03/2011, 05/2011, 06/2011, 09/2011, 12/2011, 03/2012, 06/2012, 09/2012, 09/2012, 11/2012, 12/2012, 03/2013, 06/2013, 09/2013, 11/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 09/2015, 12/0215, 03/2016, 06/2016, 09/2016, 12/2016, 03/2017, 05/2017, 09/2017, 12/2017, 03/2018, 06/2018, 10/2018, 10/2019, 10/2020, 11/2020 I. Length of Authorization Coverage will be provided as follows: o Castleman’s Disease: 4 months and may be renewed o Cytokine Release Syndrome: 4 doses only and may not be renewed o Immune Checkpoint Inhibitor related arthritis: 1 dose and may not be renewed o All other indications: 6 months and may be renewed. II. Dosing Limits A. Quantity Limit (max daily dose) [NDC Unit]: o Actemra 80 mg/4 mL vial: 1 vial per 14 days o Actemra 200 mg/10 mL vial: 1 vial per 14 days o Actemra 400 mg/20 mL vial: 2 vials per 14 days B. Max Units (per dose and over time) [HCPCS Unit]: Diagnosis Billable Units Interval (days) Rheumatoid Arthritis & Polyarticular Juvenile Idiopathic 800 28 Arthritis, NMOSD Systemic Juvenile Idiopathic Arthritis, Castleman’s Disease (NHL) & Acute Graft Versus Host Disease 800 14 (aGVHD) Cytokine Release Syndrome (CRS) 3200 1 course of therapy only Immune Checkpoint Inhibitor related arthritis 800 1 course of therapy only III. Initial Approval Criteria Site of care specialty infusion program requirements are met (refer to Moda Site of Care Policy). Moda Health Plan, Inc. Medical Necessity Criteria Page 1/19 Self-administered injectable medications are not covered when supplied in a provider’s office, clinic or facility. Coverage is provided in the following conditions: Patient is at least 18 years of age (unless otherwise specified); AND Universal Criteria 1 Patient has been evaluated and screened for the presence of latent tuberculosis (TB) infection prior to initiating treatment and will receive ongoing monitoring for presence of TB during treatment; AND Patient does not have an active infection, including clinically important localized infections; AND Must not be administered concurrently with live vaccines; AND Patient is not on concurrent treatment with another TNF-inhibitor, biologic response modifier or other non-biologic agent (i.e., apremilast, tofacitinib, baricitinib, upadacitinib, etc.), unless otherwise specified; AND Rheumatoid Arthritis † 1,3,19 Physician has assessed baseline disease severity utilizing an objective measure/tool; AND Documented moderate to severe active disease; AND Patient has had at least a 3 month trial and failed previous therapy with ONE oral disease modifying anti-rheumatic agent (DMARD) such as methotrexate, azathioprine, auranofin, hydroxychloroquine, penicillamine, sulfasalazine, leflunomide ; AND May be used alone or in combination with methotrexate or other non-biologic DMARDs Patient must try and have an inadequate response, contraindication, or intolerance to at least a three (3) month trial of Enbrel AND Humira; OR Patient is continuing treatment Juvenile Idiopathic Arthritis (JIA) † Ф 1,18 Patient is at least 2 years of age; AND Patient has active systemic (SJIA) or polyarticular (PJIA) Ф disease; AND Physician has assessed baseline disease severity utilizing an objective measure/tool; AND Patient has had at least a 1-month trial and failure (unless contraindicated or intolerant) of previous therapy with either oral non-steroidal anti-inflammatory drugs (NSAIDs) OR an oral disease-modifying anti-rheumatic agent (DMARD) (e.g., methotrexate, leflunomide, sulfasalazine, etc.); AND May be used alone or in combination with methotrexate (Note: The following applies to polyarticular (PJIA) disease only) Patient must try and have an inadequate response, contraindication, or intolerance to at least a three (3) month trial of Enbrel AND Humira; OR Patient is continuing treatment Moda Health Plan, Inc. Medical Necessity Criteria Page 2/19 Castleman’s Disease (NHL) ‡ 2 Used as a single agent; AND o Patient has unicentric disease; AND . Patient is human immunodeficiency virus (HIV)-negative and human herpesvirus-8 (HHV-8)-negative; AND . Used as second-line therapy for relapsed or refractory disease; OR o Patient has multicentric disease; AND . Used as subsequent therapy for relapsed, refractory, or progressive disease Cytokine Release Syndrome (CRS) † Ф 1,2 Patient is at least 2 years of age; AND o Patient has received or will be receiving chimeric antigen receptor (CAR) T cell therapy; AND . Tocilizumab is being ordered to have on-hand, prior to the administration of CAR-T therapy, if needed for the treatment of CRS; OR . Patient has a confirmed diagnosis of CAR-T therapy induced Grades 2-4 CRS; OR . Patient has Grade 1-4 neurotoxicity with concurrent CRS; OR o Used as supportive care in patients with refractory CRS secondary to anti-CD19 therapy (i.e., blinatumomab) Management of Immune Checkpoint Inhibitor related Inflammatory Arthritis ‡ 2,17 Patient has been receiving therapy with an immune checkpoint inhibitor (e.g. nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, cemiplimab, etc.); AND Patient has inflammatory arthritis related to their immunotherapy; AND Documented severe disease; AND Patient’s condition is refractory to high-dose corticosteroids (i.e., no improvement within 2 weeks of starting therapy) Acute Graft Versus Host Disease (aGVHD) ‡ 2,20-22 Patient has received a hematopoietic stem cell transplant; AND Used for steroid-refractory acute GVHD; AND Used in combination with systemic corticosteroids as additional therapy following no response (steroid-refractory disease) to first-line therapies Neuromyelitis Optica Spectrum Disorder (NMOSD) ‡ 23-25 Patient has a confirmed diagnosis based on the following: o Patient was found to be seropositive for aquaporin-4 (AQP4) IgG antibodies; AND . Patient has at least one core clinical characteristic §; AND . Alternative diagnoses have been excluded (e.g., multiple sclerosis, sarcoidosis, cancer, chronic infection, etc.); OR Moda Health Plan, Inc. Medical Necessity Criteria Page 3/19 o Patient was found to be seronegative for AQP-4 IgG antibodies OR has unknown AQP-4- IgG status; AND . Patient has at least two core clinical characteristics occurring as a result of one or more clinical attacks §; AND . Patient experienced ALL of the following: At least 1 core clinical characteristic must be optic neuritis, acute myelitis with LETM*, or area postrema syndrome; AND Dissemination in space (≥2 different core clinical characteristics); AND Fulfillment of additional MRI requirements, as applicable ψ; AND . Alternative diagnoses have been excluded (e.g., multiple sclerosis, sarcoidosis, cancer, chronic infection, etc.); AND Used as a single agent or in combination with immunosuppressive therapy (e.g. azathioprine, methotrexate, mycophenolate, etc.) § Core Clinical Characteristics of NMOSD 23 . Optic neuritis . Acute myelitis . Area postrema syndrome: episode of otherwise unexplained hiccups or nausea and vomiting . Acute brainstem syndrome . Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions . Symptomatic cerebral syndrome with NMOSD-typical brain lesions ψ Core Clinical Characteristics of NMOSD 23 . Acute optic neuritis: requires brain MRI showing (a) normal findings or only nonspecific white matter lesions, OR (b) optic nerve MRI with T2-hyperintense lesion or T1-weighted gadolinium- enhancing lesion extending over >1/2 optic nerve length or involving optic chiasm . Acute myelitis: requires associated intramedullary MRI lesion extending over ≥3 contiguous segments (LETM) OR ≥3 contiguous segments of focal spinal cord atrophy in patients with history compatible with acute myelitis . Area postrema syndrome: requires associated dorsal medulla/area postrema lesions . Acute brainstem syndrome: requires associated peri-ependymal brainstem lesions *LETM = longitudinally extensive transverse myelitis lesions † FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug IV. Renewal Criteria 1 Coverage can be renewed based upon the following criteria: Patient continues to meet the universal and other indication-specific relevant criteria identified in section III; AND Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include the following: serious infection, severe neutropenia, severe thrombocytopenia, severe hepatotoxicity, gastrointestinal perforation, immunosuppression, severe hypersensitivity reactions, demyelinating disorders, etc.; AND Oncology Indications Castleman’s Disease (NHL) Moda Health Plan, Inc. Medical Necessity Criteria Page 4/19 Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread Acute Graft Versus Host Disease (aGVHD) 20-22 The patient displayed a beneficial response to therapy (i.e., a complete or partial response) as determined by clinical assessment (e.g., International Bone Marrow Transplant Registry (IBMTR) scoring system, modified Glucksberg criteria, etc.) Non-Oncology Indications Rheumatoid arthritis (RA) 11-13 Disease response as indicated by improvement in signs and symptoms compared to baseline such as the number of tender and swollen joint counts, reduction of C-reactive protein, improvement of patient global assessment, and/or an improvement on a disease activity scoring tool [e.g. an improvement on a composite